Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends
원문보기
IPC분류정보
국가/구분
United States(US) Patent
등록
국제특허분류(IPC7판)
A61K-031/70
A61K-038/00
A61K-038/16
A61K-039/00
A61K-039/35
A61K-039/38
A61K-039/12
A61K-039/02
A61K-039/002
A61K-045/00
A61K-047/00
A01N-043/04
A01N-043/02
A01N-037/18
C07H-021/02
C07H-021/00
C07H-021/04
출원번호
US-0925872
(2004-08-25)
등록번호
US-7407944
(2008-08-05)
발명자
/ 주소
Agrawal,Sudhir
Kandimalla,Ekambar R.
Yu,Dong
Bhagat,Lakshmi
출원인 / 주소
Idera Pharmaceuticals, Inc.
대리인 / 주소
Keown & Zucchero, LLP
인용정보
피인용 횟수 :
27인용 특허 :
20
초록▼
The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers
The invention relates to the therapeutic use of oligonucleotides as immunostimulatory agents in immunotherapy applications. More particularly, the invention provides immunomers for use in methods for generating an immune response or for treating a patient in need of immunostimulation. The immunomers of the invention comprise at least two oligonucleotides linked at their 3' ends, internucleoside linkages or functionalized nucleobase or sugar to a non-nucleotidic linker, at least one of the oligonucleotides being an immunostimulatory oligonucleotide and having an accessible 5' end.
대표청구항▼
What is claimed is: 1. A method for generating an immune response in a vertebrate, the method comprising administering to the vertebrate an immunomer comprising at least two oligonucleotides linked at their 3' ends or internucleotide linkages or a functionalized nucleobase or sugar to a non-nucleot
What is claimed is: 1. A method for generating an immune response in a vertebrate, the method comprising administering to the vertebrate an immunomer comprising at least two oligonucleotides linked at their 3' ends or internucleotide linkages or a functionalized nucleobase or sugar to a non-nucleotidic linker, wherein at least one of the oligonucleotides is an immunostimulatory oligonucleotide having an accessible 5' end and comprising an immunostimulatory dinucleotide selected from the group consisting of C*pG, CpG* and C*pG*, wherein C is cytidine or 2'-deoxycytidine, C* is 2'deoxythymidine, arabinocytidine, 2'-deoxy-2'-substituted-arabinocytidine, 2'-O-substituted-arabinocytidine, 2'-deoxy-5-hydroxycytidine, 2'-deoxy-N4-alkyl-cytidine, 2'-deoxy-4-thiouridine or other non-natural pyrimidine nucleoside, G is guanosine or 2'-deoxyguanosine, G* is 2'-deoxy-7-deazaguanosine, 2'-deoxy-6-thioguanosine, arabinoguanosine, 2'-deoxy-2'-substituted-arabinoguanosine, 2'-O-substituted-arabinoguanosine, or other non-natural purine nucleoside, and p is an internucleoside linkage selected from the group consisting of phosphodiester, phosphorothioate, and phosphorodithioate. 2. The method of claim 1 further comprising administering a vaccine. 3. The method of claim 2, wherein the immunomer or the vaccine, or both, are linked to an immunogenic protein. 4. The method of claim 1 further comprising administering an adjuvant. 5. The method according to claim 1, further comprising administering an antigen. 6. The method according to claim 1, wherein the non-nucleotidic linker is selected from the group consisting of a linker from about 2 angstroms to about 200 angstroms in length, a metal, a soluble or insoluble biodegradable polymer bead, an organic moiety having functional groups that permit attachment to the 3'-terminal nucleoside of the oligonucleotide, a biomolecule, a cyclic or acyclic small molecule, an aliphatic or aromatic hydrocarbon, either of which optionally can include, either in the linear chain connecting the oligonucleotides or appended to it, one or more functional groups selected from the group consisting of hydroxy, amino, thiol, thioether, ether, amide, thioamide, ester, urea, and thiourea; amino acids, carbohydrates, cyclodextrins, adamantane, cholesterol, haptens antibiotics, glycerol or a glycerol homolog of the formula HO--(CH2)o--CH(OH)--(CH2)p--OH, wherein o and p independently are integers from 1 to about 6, and a derivative of 1,3-diamino-2-hydroxypropane.
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이 특허에 인용된 특허 (20)
Agrawal Sudhir ; Habus Ivan ; Kandimalla Ekambar R., Affinity-based purification of oligonucleotides using soluble multimeric oligonucleotides.
Pederson Thoru (Worcester MA) Agrawal Sudhir (Shrewsbury MA) Mayrand Sandra (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Method of site-specific alteration of RNA and production of encoded polypeptides.
Pederson Thoru (Worcester MA) Agrawal Sudhir (Shrewsbury MA) Mayrand Sandra (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Method of site-specific alteration of RNA and production of encoded polypeptides.
Agrawal,Sudhir; Kandimalla,Ekambar R.; Yu,Dong; Bhagat,Lakshmi, Modulation of immunostimulatory properties of oligonucleotide-based compounds by optimal presentation of 5' ends.
Agrawal Sudhir (Shrewsbury MA) Zamecnik Paul C. (Shrewsbury MA), Process for synthesizing oligonucleotides and their analogs adaptable to large scale syntheses.
Baumhof, Patrick; Voss, Söhnke; Kramps, Thomas; Kallen, Karl-Josef, Complexation of nucleic acids with disulfide-crosslinked cationic components for transfection and immunostimulation.
Fotin-Mleczek, Mariola; Voss, Söhnke, Composition comprising a complexed (M)RNA and a naked mRNA for providing or enhancing an immunostimulatory response in a mammal and uses thereof.
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